Factors associated with hyperglycemia and low insulin levels in children undergoing cardiac surgery with cardiopulmonary bypass who received a single high dose of methylprednisolone

OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.

Utilização do fator recombinante VIIa em paciente pediátrico com choque séptico e coagulação intravascular disseminada / The use of recombinant factor VIIa in a pediatric septic shock patient with disseminated intravascular coagulation

Relata-se o caso de uma paciente pediátrica que apresentou choque séptico e coagulação intravascular disseminada, desenvolveu sangramento grave e foi tratada com sucesso com fator recombinante VIIa.

Concentrações de adrenomedulina e relações com o eixo hipófise-adrenal e o controle glicêmico de crianças submetidas à cirurgia cardíaca com circulação extracorpórea / Adrenomedullin concentration and relationship with pituitayadrenal axis and glicemic control in children after cardiopulmonary bypass

Introdução: Adrenomedulina, peptídeo recentemente identificado, atua como mediador em diversos estados fisiológicos e patológicos, sendo expresso em inúmeros tecidos. Níveis elevados de adrenomedulina foram observados em quadros inflamatórios e sépticos, além de atividade inibitória da adrenomedulina sobre a liberação de insulina, o que poderia contribuir para a gênese e manutenção dos quadros hipeglicêmicos, situação comum em pacientes pediátricos internados em unidades de terapia intensiva, tendo sido comprovado que o controle glicêmico melhora o prognóstico nesses pacientes. O objetivo do estudo foi relacionar as concentrações de adrenomedulina com alterações de hormônios do eixo hipófise-adrenal e o controle glicêmico de crianças submetidas à cirurgia cardíaca com circulação extracorpórea (CEC) representando modelo de síndrome da resposta inflamatória sistêmica. Material e métodos: Foram incluídas 20 crianças com idade entre 11-84 meses submetidas à cirurgia cardíaca com CEC. Foram avaliadas concentrações sangüíneas de glicose, insulina, peptídeo-C, cortisol, ACTH, interleucina-6 e adrenomedulina nos tempos pré-CEC, pós-CEC, 1ºPO, 2ºPO e 3ºPO. Os resultados foram expressos em medianas e inter-quartis. Todas crianças receberam antibioticoterapia profilática (Cefuroxima 150mg/kg) e metilprednisolona (30mg/kg) na indução anestésica. Resultados: Adrenomedulina aumentou de 1,13 ng/mL (0.83 1.81) pré- CEC a 3,28 ng/mL (1.82 4.25) no 1ºPO (p=0,0005). A insulina e o peptídeo-C apresentaram queda do tempo pré-CEC ao 1ºPO: 10,9 U/mL (10.5 13.6) a 2,88 U/mL (1.68 3.46) (p= 0,0001) e 1,44 (0.93 2.08) a 0.89 ng/mL (0.58 2.06) (p=0,076), respectivamente. Houve aumento da glicemia de 86,5 mg/dL (67 88) pré-CEC a 169 mg/dL (153 201) no 1ºPO (p=0,0001). Não houve alterações significativas das concentrações de cortisol e ACTH. Após a CEC todas as concentrações de interleucina-6 encontravam-se elevadas retornando aos valores normais no 3ºPO...

Background: Adrenomedullin (AM), a recently identified vasoactive peptide, is expressed in a large number of tissues and was found to be increased in some pathophysiologic conditions such as sepsis and Systemic Inflammatory Response Syndrome (SIRS). It has been shown that AM inhibits insulin secretion by means of a direct action on pancreatic -cells thus contributing to the genesis and sustaining of hypeglicemia, a common condition in critically ill pediatric patients. Therefore, the strict control of glucose concentrations has proved beneficial and associated to decrement of morbimortality rates in adults and children. The aim of the present study was to monitor serum adrenomedullin concentration in parallel with interleukin-6, plasma glucose, insulin and C-peptide, as well as ACTH and cortisol in pediatric patients submitted to cardiac surgery and cardiopulmonary bypass (CPB) representing a SIRS model. Methods: Twenty children aged 11-84 months who underwent cardiac surgery requiring cardiopulmonary bypass were prospective studied. Blood glucose, insulin, C-peptide, adrenocorticotropic hormone, cortisol, interleukin- 6 and AM were measured immediately before cardiopulmonary bypass (BCPB), immediately after CPB, on the first (POD1), second (POD2) and third days (POD3) after surgery. Data were expressed by median values and inter quartile range. All children received profilatic antibiotic (cefuroxime 150mg/kg) and methylprednisolone (30mg/kg) during induction of anesthesia. Results: Adrenomedullin increased from 1.13 ng/mL (0.83 1.81) BCPB to 3.28 ng/mL (1.82 4.25) in POD1 (p=0.0005). Insulin dropped from 10.9 U/mL (10.5 13.6) BCPB to 2.88 U/mL (1.68 3.46) in POD1 (p=0.0000). C-peptide decreased from 1.44 (0.93 2.08) BCPB to 0.89 ng/mL (0.58 2.06) in POD1 (p=0.076). Glucose increased from 86.5 mg/dL (67 88) BCPB to 169 mg/dL (153 201) in POD1 (p=0.0000). No significant changes were observed in ACTH and cortisol levels...

Agreement and correlation of pH, bicarbonate, base excess and lactate measurements in venous and arterial blood of premature and term infants

BACKGROUND AND OBJECTIVES: Determine the extent of agreement and correlation between arterial samples and venous (obtained from a venous umbilical catheter), with respect to measurements of pH, bicarbonate, base excess and lactate, in critically ill term and premature newborns. METHODS: Arterial blood samples (0.5-1 mL) were obtained for gas analysis by radial artery puncture, and, within the limit of 5 minutes, samples were obtained from venous umbilical catheters. Bland-Altman plots were used to depict agreement between arterial and venous measurements. Limits of agreement were defined as the mean difference ± 2SD (Standard Deviation). Correlation was assessed by Pearson's method. RESULTS: A hundred and six samples (53 pairs) were taken from 53 patients for analysis of bicarbonate, pH and base excess. Lactate was analyzed in 49 pairs of samples. Differences were within the limits of agreement in 94.3 percent of pairs of samples for pH, and the same percentage was observed for bicarbonate. There was agreement in 96.2 percent of pairs for base excess, and in 91.8 percent for lactate. Mean differences were 0.03 units for pH, -1.2 mmol/L for bicarbonate, -0.24 mmol/L for base excess and 0.33 mmol/L for lactate. Pearson's correlation coefficients (r) were 0.87 for pH, 0.76 for bicarbonate, 0.86 for base excess and 0.95 for lactate. CONCLUSIONS: Although single venous values cannot be used as equivalent to arterial for assessing acid base status in newborns, venous blood samples can be used serially for monitoring trends over time.

JUSTIFICATIVA E OBJETIVOS: Determinar o grau de concordância e correlação entre amostras arteriais e as obtidas através de um cateter venoso umbilical, com relação ao pH, bicarbonato, excesso de base (BE) e lactato, em recém-nascidos prematuros e de termo, criticamente doentes. MÉTODO: Foram obtidas amostras para gasometria (0,5 - 1 mL), por punção de artéria radial, e, dentro do limite de 5 minutos, do cateter venoso umbilical. O método de Bland-Altman foi utilizado para demonstrar a concordância entre as medidas. Os limites de concordância foram definidos como a diferença média ± 2 DP. Para as correlações foi utilizado o método de Pearson. RESULTADOS: Cento e seis amostras (53 pares) de 53 pacientes foram analisadas para bicarbonato, pH e BE. Foi dosado lactato em 49 pares de amostras. Houve concordância em 94,3 por cento dos pares de amostras para o pH, e este mesmo percentual foi observado para o bicarbonato. Para o excesso de base, a concordância foi de 96,2 por cento, e de 91,8 por cento para o lactato. As diferenças médias foram 0,03 unidade para o pH, -1,2 mmol/L para o bicarbonato, -0,24 mmol/L para o excesso de base e 0,33 mmol/L para o lactato. Os coeficientes de correlação de Pearson (r) foram 0,87 para o pH, 0,76 para o bicarbonato, 0,86 para o excesso de base e 0,95 para o lactato. CONCLUSÕES: Os valores venosos isolados não podem ser usados como equivalentes aos arteriais para a avaliação do estado ácido-básico em recém-nascidos. As amostras venosas poderiam ser usadas de forma serial, para monitorizar tendências ao longo do tempo.

Cefepime restriction improves gram-negative overall resistance patterns in neonatal intensive care unit

Antibiotic restriction can be useful in maintaining bacterial susceptibility. The objective of this study was verify if restriction of cefepime, the most frequently used cephalosporin in our neonatal intensive care unit (NICU), would ameliorate broad-spectrum susceptibility of Gram-negative isolates. Nine hundred and ninety-five premature and term newborns were divided into 3 cohorts, according to the prevalence of cefepime use in the unit: Group 1 (n=396) comprised patients admitted from January 2002 to December 2003, period in which cefepime was the most used broad-spectrum antibiotic. Patients in Group 2 (n=349) were admitted when piperacillin/tazobactam replaced cefepime (January to December 2004) and in Group 3 (n=250) when cefepime was reintroduced (January to September 2005). Meropenem was the alternative third-line antibiotic for all groups. Multiresistance was defined as resistance to 2 or more unrelated antibiotics, including necessarily a third or fourth generation cephalosporin, piperacillin/tazobactam or meropenem. Statistics involved Kruskal-Wallis, Mann-Whitney and logrank tests, Kaplan-Meier analysis. Groups were comparable in length of stay, time of mechanical ventilation, gestational age and birth weight. Ninety-eight Gram-negative isolates were analyzed. Patients were more likely to remain free of multiresistant isolates by Kaplan-Meier analysis in Group 2 when compared to Group 1 (p=0.017) and Group 3 (p=0.003). There was also a significant difference in meropenem resistance rates. Cefepime has a greater propensity to select multiresistant Gram-negative pathogens than piperacillin/tazobactam and should not be used extensively in neonatal intensive care.

Terapia com hormônio de crescimento nos estados hipercatabólicos em pediatria: revisão sistemática e metanálise: [revisão] / Growth hormone therapy in pediatric hypercatabolic state: a systematic review and meta-analysis: [review]

JUSTIFICATIVA E OBJETIVOS: Avaliar a utilização do hormônio de crescimento recombinante (rhGH) em pacientes pediátricos em estado de hipercatabolismo internados em unidades de terapia intensiva pediátrica (UTIP). MÉTODO: Foram pesquisados os seguintes bancos de dados: MedLine (1990 a 2005), LILACS ( 1990 a 2005), OVID (1990 a 2006), EMBASE (1990 a 2005). Constou de estudos aleatórios controlados, em pacientes pediátricos com quadro de hipercatabolismo (queimados, sépticos) que utilizaram rhGH durante internação em UTIP. A intervenção incluía rhGH versus placebo. Os dados foram extraídos em duplicata e independentemente. A metanálise foi realizada utilizando as ferramentas estatísticas do software Review Manager, sendo utilizado o método de Mantel-Haenzel para variáveis dicotômicas e variância inversa para contínuas. RESULTADOS: Existem evidências de que a utilização do rhGH em pacientes pediátricos queimados reduziu a utilização de albumina exógena, melhora no ganho de massa muscular magra e aceleração da cicatrização dos ferimentos do local doador, sem efeito na mortalidade. Possivelmente, pode reduzir o tempo de internação. A hiperglicemia foi o evento adverso mais freqüente. CONCLUSÕES: Essa revisão sugere que a aplicação precoce do rhGH no tratamento em pacientes pediátricos com queimaduras graves tem potencial implicação na melhora clínica. Embora a literatura não dê suporte à utilização de rotina, deve-se considerar sua utilização neste grupo de pacientes, pelo menos para estudos futuros. Em pacientes sépticos, os dados são insuficientes para qualquer consideração.

BACKGROUND AND OBJECTIVES: To assess the use of recombinant human growth hormone (rhGH) in pediatric patients with hypercatabolic state in the pediatric intensive care unit. METHODS: We searched the databases of MedLine (1990 to 2005), LILACS (1990 to 2005), OVID (1990 to 2006) and EMBASE (1990 to 2005). Randomized controlled trials in pediatric patients using rhGH for hypercatabolic state (burns, sepsis) were selected. Intervention included rhGH therapy versus placebo. Data were extracted in duplicate and independently. Meta-analyses were performed using the software Review Manager statistic tools, with Mantel-Haenzel method for dichotomous outcomes and inverse variance method for continuous. RESULTS: There were evidences that rhGH in burned pediatric patients can reduce exogenous albumin requirement, with a improvement in Lean Body Mass, and accelerate site-donor wound healing, with no effects on mortality. Possibly can reduce the length of hospital stay. Hyperglycemia was the most frequently reported adverse event. CONCLUSIONS: This review suggests that the early application of rhGH to standard treatment in pediatric severe burned patients has the potential to improve some aspects from outcome. At this time, although the literature does not support routine rhGH for pediatric burn patients, consideration should be given to its use in this group, at least as an aim for further research. For use in septic patients, no proper statement can be done.